AU2018257624B2

AU2018257624B2 - Oral microbiota promoting composition and method

Info

Publication number: AU2018257624B2
Application number: AU2018257624A
Authority: AU
Inventors: Shunsheng Han
Original assignee: Knoze Jr Corp
Current assignee: Knoze Jr Corp
Priority date: 2017-04-24
Filing date: 2018-04-13
Publication date: 2021-07-08
Anticipated expiration: 2038-04-13
Also published as: KR20190141707A; JP7290869B2; AU2018257624A1; JP2020517746A; JP2021167338A; WO2019055665A1; US9795579B1; EP3609488A1; EP3609488A4; KR20220034925A; CN110520119A; US11364217B2; WO2018200223A1; US20180303781A1

Abstract

A method of promoting a desired oral microbiota in a subject to treat an allergy related respiratory condition, the method including providing an edible composition including an amino acid containing ingredient comprising L-arginine wherein the composition is provided contained and at least partially dissolved within an oral cavity of the subject for a period of at least from about 10 seconds to about an hour on a daily basis of at least two consecutive days.

Description

Oral Microbiota Promoting Composition and Method

[001] The disclosure generally relates to oral cavity

microbiota promoting compositions including sweetened prebiotic foods and methods for making and using the same. More

particularly, the disclosure relates to compositions and methods for making and using the same that may have the advantageous

effect of modulating the oral microbiota which may thereby

promote the naturally occurring health of the immune system including reducing respiratory allergic reactions.

BACKGROUND

[002] In general, the prevalence of allergic diseases has dramatically increased in recent decades and currently affects

more than sixty million people in the United States, reducing the quality of life. It is believed and has been found that the

presence of certain oral bacteria species/strains may affect the aggressiveness of response of the immune system, for example

with respect to allergies. More specifically, while not intending to be bound by any health claims, it is believed that the reduction of normally occurring oral bacteria in the

normally occurring oral microbiota, for example, by aggressive dental hygiene practices, may serve to make non-pathogenic

antigens, such as pollen, more prevalent and visible to the

immune system. It is further believed, that as a result, non

pathogenic antigens, such as those related to allergens may be more readily targeted by the immune system, leading to exacerbated allergic reactions.

[003] For example, oral hygiene hypothesis (OHH) is one

aspect of a more general hygiene hypothesis (HH), which was

proposed more than two decades ago ( see Strachan, D.P. "Hay

1 SUBSTITUTE SHEET (RULE 26) fever, hygiene, and household size", British Medical Journal 299, 1259-1260 (1989)) to explain the rise in allergic diseases.

Numerous scientific studies have since provided support for HH, generally showing a relation between increased exhibition of

allergies in association with modern social practices, such as

formula infant feeding, antibiotic use, urban living, and reduction in family size (see e.g., Okada, H., Kuhn, C.,

Feillet, H. & Bach, J.F., "The hygiene hypothesis for autoimmune and allergic diseases: an update" Clin. Exp. Immunol. 160, 1-9

(2010)). Although the molecular mechanisms of immune system modulation by gut microbiota are well understood, efforts to reduce allergic reactions through microbial intervention, such

as by the use of probiotics have shown inconsistent results.

[004] Extensive oral hygiene practices, according to oral hygiene hypothesis (Han, CS., "A specific hygiene hypothesis"

Med. Hypotheses 2016 Aug; 93:146-149), are believed to cause

related the exacerbation of naturally occurring respiratory allergies, such as allergic rhinitis (AR), one of the most

common allergic conditions.

[005] There is therefore a need for a composition including an oral cavity microbiota promoting substance and method of

using the same that has the effect of promoting a healthy oral

microbiota that promotes the healthy operation of the immune system which may have the functional effect of promoting an improved response to allergens.

[006] It is an object of the invention to provide a

composition including an oral cavity microbiota promoting substance and method of using the same that has the effect of

promoting a healthy oral microbiota that promotes the healthy

2 SUBSTITUTE SHEET (RULE 26) operation of the immune system which may have the functional effect of promoting an improved response to allergens.

SUMMARY

[007] A use of a product in the preparation of a medicament for

promoting a desired oral microbiota to treat an allergy related

respiratory condition in a subject in need of such treatment

comprising: providing a prebiotic edible composition comprising an

amino acid containing ingredient comprising individual molecules of

L-arginine and a sugar containing ingredient, the sugar comprising

one or more of monosaccharides, disaccharides, oligosaccharides, and

polysaccharides; removing a biofilm from surfaces within an oral

cavity by heating the inside of the oral cavity to a temperature of

about 37 deg C. to about 55 deg C.; wherein following removal of the

biofilm, the composition is provided contained and at least partially

dissolved within an oral cavity of the subject for a period of at

least from about 10 seconds to about an hour on a daily basis of at

least two consecutive days to promote an increased concentration of

selected oral microbiota, the selected microbiota comprising

Veillonella and Streptococcus, to thereby treat an allergy related

respiratory condition.

DETAILED DESCRIPTION

[008] The following detailed description is merely exemplary in

nature and is not intended to limit the described embodiments or the

application and uses of the described embodiments. As used herein,

the word "exemplary" or "illustrative" means "serving as an example,

instance, or illustration.'' Any implementation described herein as "exemplary" or "illustrative" is not necessarily to be construed as

preferred or advantageous over other implementations. All of the

implementations described below are exemplary implementations

provided to enable persons skilled in the art to practice the

disclosure and are not intended to limit the scope of the appended

claims. Furthermore, there is no intention to be bound by any expressed

or implied theory presented in the preceding technical field,

background, brief summary or the following detailed description.

[009] It is believed, and has been found that according to the oral hygiene hypothesis (OHH) noted above, that persistent and intensive hygiene practices, together with other life events, such as fever and/or antibiotic usage, will likely change the oral microbiota of an individual. The oral cavity is a complex environment with many different biological niches, such as the tongue, gum, and teeth. Normally occurring microbiota associated with these niches are different and are believed to have a different effect on normal functioning of the immune system.

[0010] Likewise, it is believed, and has been unexpectedly found, that the introduction of selected microbiota-promoting

substances into the oral cavity in a controlled manner, may

promote desired naturally occurring oral bacteria species/strains, which may in turn have an associated effect of

modulating or reducing the intensity of certain types of

allergic reactions, including those associated with allergic rhinitis (AR) one of the most common allergic reactions

including symptoms such as any combination of a runny or stuffy nose, sneezing, itchy/red eyes, coughing, and congestion.

[0011] While not intending to be bound by any particular

theory of operation, and making no specific health claims, it is believed that oral microbiota interact with the host largely

through metabolites produced by its relevant bacterial members.

Those metabolites, such as but not limited to short chain fatty

acid, may influence the function of multiple biologic systems and organs, such as the immune system. Missing or severe

reduction of the relevant bacteria may cause malfunctioning of

the immune system, such as causing over sensitivity to allergens.

4 SUBSTITUTE SHEET (RULE 26)

[0012] Therefore, it is believed that the immune system

response to the allergen may be modulated such that the

associated allergic reaction symptoms are suppressed relative to what an allergic reaction may be with an unhealthy level of or

different microbiota. It is further believed and evidence

suggests that over time, as a result of promoting a healthy oral microbiota with selected microbiota-promoting substances that

the immune system may function in a healthy manner with a healthy response to allergens.

[0013] Furthermore, due to the connectivity among mouth and respiratory duct and lungs, a healthy oral microbiota may lead

to a healthy microbiota in the lungs as well. Eventually the

method may benefit the healthy functioning of the immune system which may in turn have a healthy response not only to allergic

rhinitis but also the relevant diseases in the lungs, such as

asthma.

[0014] In one embodiment, an oral microbiota promoting

composition may be provided into an oral cavity that may have the effect of promoting desired microbiota within an oral cavity.

[0015] In another embodiment, a method of applying an oral microbiota promoting composition (prebiotic) may be provided

that may have the effect of promoting desired microbiota within an oral cavity and have the desired functional effect of

treating a respiratory condition including allergic rhinitis.

[0016] In one embodiment, a method of applying an oral

microbiota promoting composition may include multiple instances

of introduction of the composition into the oral cavity (mouth)

5 SUBSTITUTE SHEET (RULE 26) in the form or a solid, powder, paste, or liquid in the amount of about 1 gm to about 500 gms at one time or multiple times in fractional amounts. Where the oral microbiota promoting composition is in the form of liquid, the method may include dissolving the composition in a liquid

[0017] In another embodiment, a method of applying an oral

microbiota promoting composition may include swallowing the

composition following introduction of the composition into the oral cavity and following a period of retaining the composition within the mouth for a select period of time including e.g., chewing, gargling, and/or sublimating (dissolving) the

composition while within the oral cavity.

[0018] In another embodiment, a method of applying an oral microbiota promoting composition may include removing the

composition following introduction into the oral cavity by

expelling (e.g., pulling out or spitting-out) the microbiota promoting composition following a period of retaining the

composition within the mouth.

[0019] In another embodiment, a method of applying an oral

microbiota promoting composition may include retaining the microbiota promoting composition within the oral cavity from about 10 seconds to about an hour, more preferably, from about 5

minutes to about 30 minutes on a daily basis for a period of about 2 days to about 60 days.

[0020] In another embodiment, a method of applying an oral microbiota promoting composition may include introducing the

microbiota promoting composition for relatively short periods

several times a day, for example from about 1 second to about 30

6 SUBSTITUTE SHEET (RULE 26) seconds, each from about 3 to about 10 times a day for a period of about 2 days to about 60 days.

[0021] In another embodiment, a method of applying an oral microbiota promoting composition may include extending the

periods of introduction of the microbiota promoting composition into the oral cavity, for example, from about every 3 days to

about every 10 days, including stopping the introduction of the

composition following the disappearance of allergy symptoms.

[0022] In another embodiment, a method of applying an oral

microbiota promoting composition may include at least partially removing a mucosal film (biofilm) from within the oral cavity prior to or while administering the microbiota promoting

composition to the oral cavity.

[0023] It will he appreciated that the hiofilm may be at

least partially removed by raising the whole body temperature

for a short time, for example, with conventional biological or physical means.

[0024] In a related embodiment, the biofilm may be at least partially removed by rinsing out (optionally including scrubbing

or rubbing) the oral cavity (mouth) with a heated water

containing liquid, such as water, at a temperature of from about 90 to about 130 degrees Fahrenheit prior to applying the oral

microbiota promoting composition to the oral cavity. It will be appreciated that rinsing with a hot water containing fluid as

noted may advantageously at least partially remove a biofilm from surfaces within the oral cavity, thereby improving the

operation of the oral microbiota promoting composition. The

oral rinsing may include periodic rinsing, for example, each for

7 SUBSTITUTE SHEET (RULE 26) about 10 seconds to about 30 seconds over a period of from about

5 to about 15 minutes.

[0025] In another embodiment, a method of applying an oral microbiota promoting composition may include at least one of

brushing and rubbing portions of the oral cavity with the hot water containing fluid at a temperature of from about 100 to

about 130 degrees Fahrenheit including at least the tongue, for

example, with at least one of a brush, such as a toothbrush, and/or a wet cloth.

[0026] In another embodiment, the oral microbiota promoting composition may be formulated into oral dosage forms such as tablets, caplets, and capsules, or a powder formulation or that

may be dissolved in a liquid, for example diluted in a liquid having a ratio of from about 1:1 to about 1:500 with respect to

either weight or volume of the liquid (e.g., the liquid being

larger number).

[0027] In another embodiment, the oral microbiota promoting

composition may be formulated or manufactured as a chewing gum or candy, or other edible carrier, for example as an additive

having a ratio of from about 1:1 to about 1:500 with respect to either weight or volume of the edible carrier (e.g., larger number) .

[0028] In another embodiment, the oral microbiota promoting composition may be formulated as an additive to an oral hygiene

product acting as a carrier, such as toothpaste or mouthwash, the microbiota promoting composition having a ratio of from about 1:1 to about 1:500 with respect to either weight or volume

of the oral hygiene product.

8 SUBSTITUTE SHEET (RULE 26)

[0029] In another embodiment, in a method of manufacturing an oral microbiota promoting composition may be formulated having

an edible foodstuff as a carrier, the microbiota promoting composition having a ratio of from about 1:1 to about 1:500 with

respect to either weight or volume of the edible foodstuff.

[0030] In one embodiment, the desired microbial

species/strains promoted in the oral cavity by the oral

microbiota promoting composition may be naturally occurring within the oral cavity and/or may be provided separately or within the oral microbiota promoting composition.

[0031] In a related embodiment, the desired microbial species/strains are present in the oral cavity or in the oral

microbiota promoting composition at a level of from about 1000 to about 1,000,000,000 living cells.

[0032] It will be appreciated that the desired microbial

species/strains are naturally occurring and/or may be obtained commercially and handled in accordance with any applicable

safety requirements,

[0033] In another embodiment, the desired microbial

species/strains promoted in the oral cavity by the oral

microbiota promoting composition may include at least a first microbial species that can attach to surfaces (e.g., teeth,

tongue, mouth) within the oral cavity and at least one second microbial species that may attach to the same or different

surfaces and/or may attach to the at least first microbial species.

9 SUBSTITUTE SHEET (RULE 26)

[0034] In a related embodiment, the at least a first and

second microbial species may produce a product, such as a sugar containing moiety, that may be metabolized by the other of the at least a first and second microbial species.

[0035] In one embodiment, one of the desired microbial members promoted within the oral cavity promoted by the oral

microbiota promoting composition may include one or more live

bacterium with lactate fermenting capability such as, but not limited to Veillonella, which further may include one or more of associated species, such as, but not limited to, V. Dispar and V. Parvula.

[0036] In one embodiment, one of the desired microbial

species/strains promoted within the oral cavity promoted by the oral microbiota promoting composition may include one or more

live lactic acid producing bacterium such as but not limited to

Streptococcus including one or more of associated species, such as, but not limited to, S. salivarius and S. thermophilus.

[0037] In a related embodiment, the desired microbial species/strains promoted within the oral cavity by the oral

microbiota promoting composition may include at least one live lactic acid producing bacterium and at least one live lactate fermenting bacterium such as, but not limited to, respectively,

Veillonella and Streptococcus and their respectively associated preferred species stated above.

[0038] In another embodiment, an oral microbiota promoting composition is provided that includes at least one amino acid

or amino acid containing substance including at least L

arginine. The at least one amino acid may further or

10 SUBSTITUTE SHEET (RULE 26) alternately include at least one of L-cysteine, DL-aspartic acid, L-glutamic acid, L-serine and L-tyrosine including phosphates, salts, acids, and enzymes comprising the same.

[0039] In a related embodiment, the at least one amino acid,

may be present in the oral microbiota promoting composition at a weight percent level of from about 0.1 wt. % to about 99.9 wt.

%, more preferably, from about 5 wt % to about 95 wt %, even

more preferably from about 20 wt % to 80 wt %.

[0040] In another embodiment, an oral microbiota promoting composition is provided that includes at least one sugar containing substance and at least one amino acid containing substance. The at least one sugar containing substance may

include at least one monosaccharide, disaccharide, oligosaccharide, and polysaccharide. .

[0041] Exemplary monosaccharides may include but are not

limited to aldohexoses such as but not limited to mannose including associated isomers, phosphates, salts, acids, and

enzymes comprising the same.

[0042] Exemplary disaccharides may include but are not

limited to disaccharides including at least one of galactose and

glucose, such as but not limited to lactose, sucrose, malibiose, maltose, cellobiose and trehalose (also known as mycose or

tremalose) including associated isomers, phosphates, salts, acids, and enzymes comprising the same.

[0043] Exemplary oligosaccharides may include but are not limited to trisaccharides including at least one or more of

galactose, glucose, and fructose, such as but not limited to

11 SUBSTITUTE SHEET (RULE 26) raffinose (also known as melitose), stachyose, and verbascose, including associated isomers, phosphates, salts, acids, and enzymes comprising the same.

[0044] Further, Exemplary polysaccharides may include but are

not limited to one or more polysaccharide polymers, such as, but not limited to polysaccharides including malotriose units,

including but not limited to pullulan, and fructose polymers,

such as, but not limited to inulin and further including associated isomers, phosphates, salts, acids, and enzymes comprising the same.

[0045] In a related embodiment, the at least one disaccharide may be present in the oral microbiota promoting composition at a

weight percent level of from about 0.1 wt. % to about 99.9 wt. %, more preferably, from about 5 wt % to about 95 wt %, even

more preferably from about 20 wt % to 80 wt %.

[0046] In a related embodiment, the at least one oligosaccharide may be present in the oral microbiota promoting

composition at a weight percent level of from about 0.1 wt. % to about 99.9 wt. %, more preferably, from about 5 wt % to about 95

wt %, even more preferably from about 20 wt % to 80 wt %.

[0047] In a related embodiment, the at least one polysaccharide may be present in the oral microbiota promoting

wt %, even more preferably from about 20 wt % to 80 wt%.

12 SUBSTITUTE SHEET (RULE 26)

[0048] In another embodiment, the oral microbiota promoting

composition may include at least one prebiotic fiber. Exemplary prebiotic fibers may include but are not limited to inulin.

[0049] In a related embodiment, the at least one prebiotic

fiber may be present in the oral microbiota promoting composition at a weight percent level of from about 0.1 wt. %- to

about 99.9 wt. %, more preferably, from about 5 wt % to about 95

wt %, even more preferably from about 10 wt % to 30 wt %.

[0050] In another embodiment the oral microbiota promoting composition may include additives such as one or more of carbohydrates, amino acids, salts, flavorants, proteins, surfactants, emulsifiers, flavonoids, alcohols, synthetic

sweeteners, food preserving agents, and combinations thereof.

[0051] In one embodiment, the oral microbiota promoting

composition may further include conventional foodstuffs such as

one or more of brown sugar, syrup, honey, chocolate, nuts, almonds, spices, cinnamon, and vanilla.

[0052] In a specific exemplary embodiment, an example of making an edible Foodstuff oral microbiota promoting composition

is provided below in Example 1:

[0053] Example 1:

[0054] 1 cup raffinose

[0055] 1 cup trehalose

[0056] 2 tablespoons mannose

[0057] 1 cup lactose

13 SUBSTITUTE SHEET (RULE 26)

[0058] 4 cup maltose

[0059] 4 cup arginine

[0060] 2 tablespoons pullulan

[0061] 1 cup inulin

[0062] 1 cup dark brown sugar

[0063] b cup corn syrup

[0064] 4 cup honey

[0065] 1 cup milk chocolate

[0066] 1 cup chocolate chips

[0067] t4 cup toasted almonds (small chips)

[0068] ; tablespoon cinnamon

[0069] 1/4 tablespoon vanilla extract

[0070] In one embodiment, the above ingredients may be

admixed and heated to a temperature sufficient to melt or liquefy, preferably avoiding boiling for an extended period and then poured into a container to cool.

[0071] In another embodiment, live bacterium, in accordance

with safety requirements or limitations, may be added following cooling (e.g., as a coating). It will be appreciated that adding the bacterium may be limited by applicable safety

precautions and may reduce the shelf life of the product.

[0072] Although the embodiments of this disclosure have been described with respect to certain exemplary embodiments, it is

to be understood that the specific embodiments are for purposes of illustration and not limitation, as other variations will

occur to those of skill in the art.

14 SUBSTITUTE SHEET (RULE 26)

Claims

1. A use of a product in the preparation of a medicament for promoting a desired oral

microbiota to treat an allergy related respiratory condition in a subject in need of such

treatment comprising:

providing a prebiotic edible composition comprising an amino acid containing

ingredient comprising individual molecules of L-arginine and a sugar containing ingredient,

the sugar comprising one or more of monosaccharides, disaccharides, oligosaccharides, and

polysaccharides;

removing a biofilm from surfaces within an oral cavity by heating the inside of the

oral cavity to a temperature of about 37 deg C. to about 55 deg C.;

wherein following removal of the biofilm, the composition is provided contained and

at least partially dissolved within an oral cavity of the subject for a period of at least from

about 10 seconds to about an hour on a daily basis of at least two consecutive days to

promote an increased concentration of selected oral microbiota, the selected microbiota

comprising Veillonella and Streptococcus, to thereby treat an allergy related respiratory

condition.

2. The use of claim 1, wherein the composition is provided in a carrier.

3. The use of claim 2, wherein the carrier comprises a solid, powder or liquid.

4. The use of claim 2, wherein the carrier comprises one or more of a chewable tablet, an

edible capsule, and a hygienic paste, and an edible food.

5. The use of claim 1, wherein the composition is provided within the oral cavity

from a period of from about 2 consecutive days to about 60 consecutive days.

6. The use of claim 1, wherein heating the inside of the oral cavity comprises periodic

oral rinsing with a heated liquid, each rinsing for about 10 seconds to about 1 minute over a

period of from about 5 to about 15 minutes.

7. The use of claim 1, wherein removal of a biofilm comprises heating the inside of the

oral cavity including at least one of rinsing, brushing, and rubbing the oral cavity with a

heated liquid.

8. The use of claim 1, wherein the at least one amino acid further comprises at least one

of L-cysteine, DL-aspartic acid, L-glutamic acid, L-serine, and L-tyrosine.

9. The use of claim 1, wherein the amino acid containing ingredient is present in the

composition at a weight percent level of from about 0.1 wt.% to about 99.9 wt.%.

10. The use of claim 1, wherein the composition further comprises a sugar containing

ingredient, the sugar comprising one or more of monosaccharides, disaccharides,

oligosaccharides, and polysaccharides.

11. The use of claim 10, wherein the sugar comprises one or more of mannose, lactose,

malibiose, maltose, cellobiose, trehalose, raffinose.

12. The use of claim 10, wherein the composition further comprises polysaccharide

polymers.

13. The use of claim 12, wherein the polysaccharide polymers comprise one or more of

pullulan and inulin.

14. The use of claim 10, wherein the sugar is present in the composition at a weight

percent level of from about 0.1 wt. % to about 99.9 wt. %.

15. The use of claim 10, wherein the sugar is present in the composition at a weight

percent level of from about 0.5 wt. % to about 95 wt. %.

16. The use of claim 10, wherein at least one of the composition and oral cavity further

comprises live bacterium comprising a lactic acid producing bacterium and a lactate

fermenting bacterium.

17. The use of claim 1, wherein the sugar comprises one or more of mannose, lactose,

malibiose, maltose, cellobiose, trehalose, raffinose.

18. The use of claim 1, wherein at least one of the edible composition and oral cavity

further comprises live bacterium comprising a lactic acid producing bacterium and a lactate

fermenting bacterium.